Cholesterol Lowering and CV Risk: Meta-analyses. On-Treatment LDL and CHD Events in Statin Trials 2 Adapted from Rosenson RS. Expert Opin Emerg Drugs.

Slides:

Advertisements

Similar presentations

Statin Landmark Trials Across the Spectrum of Risk: Secondary CV Prevention.

Advertisements

Atorvastatin in Type 2 diabetics on dialysis: 4D Study 1255 T2DM patients on dialysis for 8.3 mo; 29% with prior MI or revascularization or CHD; 35% CHF;

Protecting the heart and the kidney: Implications from the SHARP trial Dr. Christina Reith University of Oxford United Kingdom.

The case for intensive lipid management: The opportunities and issues for cardiologists Prof. John Betteridge University College London Slide lecture prepared.

P H Y S I C I A N S ’ A C A D E M Y F O R C A R D I O V A S C U L A R E D U C A T I O N Insights from clinical trials: The unassailable case for LDL-c.

Lipid Disorders and Management in Diabetes

The efFects of Pharmacological management of lipids in patients with CKD Andrew Monson FY1 18/9/14.

Prescribing Information is available at the end of this presentation NHS Surrey Lipid Guidelines Dr Adam Jacques Ashford & St.

Benefits of intensive multiple risk factor intervention.

Managing the late consequences of CHD: What is the evidence for lipid management Prof Philip Barter The Heart Research Institute Sydney, Australia Slides.

On-Treatment LDL and CHD Events in Statin Trials 2 Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9: LaRosa JC et al. N Engl J Med. 2005;352:

TNT: Study Design Treating to New Targets 2 5 years 10,001 Patients Clinically evident CHD LDL-C 130  250 mg/dL following up to 8-week washout and 8-week.

Cholesterol quintile (mg/dL)

Slide Source: Lipids Online Slide Library Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) 5804 patients aged 70–82.

How Aggressive do we get on Lipids? Christopher Cannon, M.D. Senior Investigator, TIMI Study Group Cardiovascular Division, Brigham and Women’s Hospital,

Lancet : doi: /S (08)60104-X Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from.

TC LDL- C HDL- C Nonfatal MI/CHD death CHD death All- cause mortality *As compared to placebo. † P= CARE: Effect of Lipid Lowering on Lipid Values.

LIPID LOWERING IN T2D (The Lower the Better?) CONS… TARGETING HARD CVD END POINTS Charles SAAB MD Consultant Endocrinologist DCRP Sacre-Coeur University.

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Ungroup once.

VBWG IDEAL: The Incremental Decrease in End Points Through Aggressive Lipid Lowering Study.

Simvastatin in Patients With Prior Cerebrovascular Disease: HPS

(N=488) Simvastatin in Patients With Prior Cerebrovascular Disease: HPS *29% RRR, p=0.001 Heart Protection Study Collaborative Group. Lancet. 2004;363:

Lipids: Is Lower Better For Diabetic Patients? Prof. Samir Helmy Assaad -Khalil Department of Internal Medicine Unit of Diabetes, Lipidology & Metabolism.

HYPERLIPIDAEMIA. 4S 4444 patients –Hx angina or MI –Cholesterol Simvastatin 20mg (10-40) vs. placebo FU 5 years  total cholesterol 25%;  LDL.

Who should have statins 18 th March Nonfatal MI CHD death Any major coronary event CABG PTCA Unspecified Any coronary revascularisation.

Lipid Lowering Substudy Trial of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial JAMA 2002;288: ALLHAT- LLT.

Slide Source: Lipids Online Slide Library Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

Slides prepared and presented by

VBWG HPS. Lancet. 2003;361: Gæde P et al. N Engl J Med. 2003;348: Recent statin trials: Reduction in primary outcome in patients with diabetes.

The concept of Diabetes & CV risk: A lifetime risk challenge The Clinical Significance of LDL-Cholesterol: No Longer a Hypothesis? John J.P. Kastelein,

Slide Source: Lipids Online Slide Library Collaborative Atorvastatin Diabetes Study (CARDS) Type 2 diabetes mellitus Men and women.

HPS: Heart Protection Study Purpose To determine whether simvastatin reduces mortality and vascular events in patients with and without coronary disease,

The Prospective Pravastatin Pooling Project L I P I D CARECARE PPP Project Investigators Am J Cardiol 1995; 76:899–905.

WOSCOPS: West Of Scotland Coronary Prevention Study Purpose To determine whether pravastatin reduces combined incidence of nonfatal MI and death due to.

SPARCL Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial.

LIPID: Long-term Intervention with Pravastatin in Ischemic Disease Purpose To determine whether pravastatin will reduce coronary mortality and morbidity.

The overwhelming case for LDL-C lowering

Amarenco P, Labreuche J. Lancet Neurol 2009;8:

4S: Scandinavian Simvastatin Survival Study

Cholesterol Treatment Trialists’ (CTT) Collaboration Slide deck

Number of participants with diabetes by trial Cholesterol Treatment Trialists' (CTT) Collaborators Lancet 2008;371:

Baseline characteristics and eligibility criteria of participating trials Cholesterol Treatment Trialists’ (CTT) Collaborators Lancet 2005;366:

Date of download: 6/26/2016 From: Lipid-Lowering Therapy in Persons With Chronic Kidney Disease: A Systematic Review and Meta- analysis Ann Intern Med.

Double-blind, randomized trial in 4,162 patients with Acute Coronary Syndrome

Statins in risk reduction Vasil Velchev MD, PhD St.Anna University Hospital, Sofia.

Over Time Additional Risk Factors Can Progress: Effect of Cholesterol and BP on CHD Risk in MRFIT Trial

Baseline characteristics of HPS participants by prior cerebrovascular disease.

Cholesterol Treatment Trialists’ (CTT) Collaboration Slide deck.

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from participants in 26 randomised trials Lancet 2010;

Christie M. Ballantyne, MD

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Ungroup once.

Cholesterol Treatment Trialists’ (CTT) Collaboration Slide deck

Reducing Adverse Outcomes after ACS in Patients with Diabetes Goals

2013 ACC/AHA cholesterol treatment guidelines

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised.

Cholesterol Lowering and CV Risk: Meta-analyses

Cholesterol Treatment Trialists’ (CTT) Collaboration Slide deck

HDL cholesterol and cardiovascular risk Epidemiological evidence

First time a CETP inhibitor shows reduction of serious CV events

TNT: Baseline and final LDL cholesterol levels

Dyslipidemia and Cardiovascular disease prevention 여수제일병원 이 우 석.

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised.

2013 ACC/AHA cholesterol treatment guidelines

Potential mechanisms whereby statins may reduce the risk of stroke

Cause of death Treatment-arm events, % (n=45 054)

Delahoy PJ, et al. Clin Ther 2009;31:236-44

PROSPER: trial design

Simvastatin in Patients With Prior Cerebrovascular Disease: HPS

FIELD: Primary outcome

Presentation transcript:

Cholesterol Lowering and CV Risk: Meta-analyses

On-Treatment LDL and CHD Events in Statin Trials 2 Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9: LaRosa JC et al. N Engl J Med. 2005;352: WOSCOPS - Rx 4S - Rx LIPID - Rx 4S - PBO CARE - Rx LIPID - PBO CARE - PBO WOSCOPS - PBO AFCAPS - PBO AFCAPS - Rx WOSCOPS - Rx (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) Secondary Prevention Primary Prevention 200 (5.2) ASCOT - PBO ASCOT - Rx PROVE-IT - PRA PROVE-IT - ATV80 TNT - ATV10 Event rate (%) LDL-C achieved, mg/dL (mmol/L) 70 (1.8) HPS - PBO HPS - Rx TNT - ATV80

Second Cycle of the CTT Meta-analysis: Proportional Effects on Major Vascular Events Per Mmol/L LDL-C Reduction Relative risk (CI) per mmol/L LDL-C reduction Statin/more betterControl/less better Statin vs. control More vs. less statin First cycle (14 trials) A to Z PROVE-IT ALLIANCE ASPEN TNT 4D MEGA IDEAL SEARCH JUPITER GISSI-HF AURORA 5883 (3.1) 257 (7.2) 406 (11.3) 254 (5.4) 114 (2.7) 889 (4.0) 144 (9.0) 102 (0.5) 938 (5.2) 1347 (3.6) 105 (0.5) 172 (2.2) 362 (8.1) 7467 (4.0) 282 (8.1) 458 (13.1) 293 (6.4) 136 (3.3) 1164 (5.4) 162 (10.1) 140 (0.7) 1106 (6.3) 1406 (3.8) 194 (1.0) 174 (2.2) 368 (8.3) 0.78 ( ) Subtotal (21 trials) 7136 (2.8)8934 (3.6) 0.79 ( ) P < Subtotal (5 trials) 3837 (4.5)4416 (5.3) 0.72 ( ) P < Total (26 trials)10973 (3.2)13350 (4.0) 0.78 ( ) P < Difference between more vs. less and statin vs. control: c 1 2 = 4.5, p= % or95% CI No. of events (% pa) Statin/moreControl/less Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:

Second Cycle of the CTT Meta-analysis: More vs Less Statin—Proportional Effects on Major Vascular Events Per Mmol/L LDL-C Reduction Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:

Nonfatal MI CHD death Any major coronary event CABG PTCA Unspecified Any coronary revascularization Ischemic stroke Hemorrhagic stroke Unknown stroke Any stroke Any major vascular event (all 21 trials) 2310 (0.9%) 1242 (0.5%) 3380 (1.3%) 816 (0.3%) 601 (0.2%) 1686 (0.6%) 3103 (1.2%) 987 (0.4%) 188 (0.1%) 555 (0.2%) 1730 (0.7%) 7136 (2.8%) 3213 (1.2%) 1587 (0.6%) 4539 (1.7%) 1126 (0.4%) 775 (0.3%) 2165 (0.8%) 4066 (1.6%) 1225 (0.5%) 163 (0.1%) 629 (0.2%) 2017 (0.8%) 8934 (3.6%) 0.74 ( ) 0.80 ( ) 0.76 ( ) P < ( ) 0.78 ( ) 0.76 ( ) 0.76 ( ) P < ( ) 1.10 ( ) 0.88 ( ) 0.85 ( ) P < ( ) P < Second Cycle of the CTT Meta-analysis: Statin vs Control—Proportional Effects on Major Vascular Events Per Mmol/L LDL-C Reduction 5 No. of events (% pa) StatinControl Relative risk (CI) per mmol/L LDL-C reduction Statin betterControl better 99% or 95% CI Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:

Meta-analysis of Statin Trials and Fatal and Nonfatal Stroke 6 Amarenco P et al. Lancet Neurol. 2009;8: N = 165,732 Log-scale Study 0.1 Active group (%) Control group (%) RR (95% CI) Total: P < (heterogeneity: I 2 = 7.3%, P = 0.36) SEARCH JUPITER ASPEN MEGA IDEAL TNT ALLIANCE CARDS PROVE-IT A TO Z ASCOT-LLA ALLHAT-LLT GREACE HPS (with no prior CVD) PROSPER MIRACL GISSI AFCAPS/TexCAPS LIPID (with no prior CVD) Post-CABG CARE (with no prior CVD) WOSCOPS SSSS Sub-total: P < (heterogeneity: I 2 = 26.6%, P = 0.12) SPARCL HPS (with prior CVD LIPID (with prior CVD) CARE (with prior CVD) Sub-total: P = 0.03 (heterogeneity: I 2 = 0.8%, P = 0.39) Primary prevention of stroke (0.77, 1.08) 0.52 (0.34, 0.78) 0.89 (0.56, 1.40) 0.83 (057,1.20) 0.87 (0.70, 1.08) 0.76 (0.60, 0.96) 0.90 (0.58, 1.42) 0.53 (0.31, 0.90) 1.09 (0.59, 2.01) 0.79 (0.48, 1.29) 0.73 (0.56, 0.96) 0.91 (0.76, 1.09) 0.53 (0.24, 1.18) 0.67 (0.57, 0.77) 1.04 (0.82, 1.31) 0.50 (0.25, 1.00) 1.05 (0.56, 1.96) 0.82 (0.41, 1.67) 0.84 (0.67, 1.05) 1.12 (0.58, 2.18) 0.67 (0.44, 1.01) 0.90 (0.61, 1.34) 0.72 (0.51, 1.01) 0.81 (0.75, 0.87) Secondary prevention of stroke 0.82 (0.77, (0.73, (0.81, 1.21) 0.72 (0.46, 1.12) 0.68 (0.37, 1.25) 0.88 (0.78, 0.99) RR (95% CI)

Meta-analysis of Statin Trials and Stroke Mortality Amarenco P et al. Lancet Neurol. 2009;8: SEARCH JUPITER CARDS ALLHAT-LLT GREACE HPS PROSPER MIRACL GISSI LIPID CARE WOSCOPS SSSS Sub-total: P = 0.18 (heterogeneity: I 2 = 0%, P = 0.48) Study Active group (%) Control group (%) RR (95% CI) Primary prevention of stroke (0.60, 1.21) 0.50 (0.13, 2.00) 0.14 (0.02, 1.15) 0.95 (0.65, 1.38) 0.33 (0.01, 8.17) 0.81 (0.62, 1.05) 1.58 (0.81, 3.09) 1.51 (0.25, 9.02) 1.00 (0.25, 3.98) 0.81 (0.46, 1.43) 4.99 (0.58, 42.70) 1.50 (0.42, 5.30) 1.17 (0.54, 2.52) 0.90 (0.76, 1.05) RR (95% CI) Secondary prevention of stroke SPARCL Total: P = 0.10 (heterogeneity: I 2 = 8.1%, P = 0.36) (0.36, 0.97) 0.87 (0.73, 1.03) Log-scale

Stroke Risk and LDL Lowering in Statin Trials 8 Each 1 mmol (39 mg) LDL-C reduction reduced the risk of stroke by 21% (95% CI, 6.3–33.5%; p<0.009) N = 165,732 Amarenco P et al. Lancet Neurol. 2009;8: Between Group Difference in LDL-Cholesterol Reduction, % (active minus control groups) Relative Risk of Stroke in Active vs Control Groups (non-log scale) LIPID TNT GISSI PROSPER PROVE-IT Post-CABG SPARCL-CS (-) SPARCL SPARCL-CS (+) WOSCOPS ASPEN ALLHAT-LLT SEARCH IDEAL ALLIANCE CARE CARDS GREACE JUPITER MIRACL MEGA A to Z AFCAPS/TexCAPS HPS ASCOT-LLA SSSS 0 0

Statin/more better Control/less better Vascular causes Nonvascular CHD Other cardiac All cardiac Ischemic stroke Hemorrhagic stroke Unknown stroke Stroke Other vascular Any vascular Cancer Respiratory Trauma Other nonvascular Any nonvascular Unknown death Any death 1887 (0.5%) 1446 (0.4%) 3333 (0.9%) 153 (0.0%) 102 (0.0%) 228 (0.1%) 483 (0.1%) 404 (0.1%) 4220 (1.2%) 1781 (0.5%) 224 (0.1%) 127 (0.0%) 811 (0.2%) 2943 (0.8%) 479 (0.1%) 7642 (2.1%) 2281 (0.6%) 1603 (0.4%) 3884 (1.1%) 139 (0.0%) 89 (0.0%) 273 (0.1%) 501 (0.1%) 409 (0.1%) 4794 (1.3%) 1798 (0.5%) 237 (0.1%) 127 (0.0%) 832 (0.2%) 2994 (0.8%) 539 (0.1%) 8327 (2.3%) 0.80 ( ) 0.89 ( ) 0.84 ( ) 1.04 ( ) 1.12 ( ) 0.85 ( ) 0.96 ( ) 0.98 ( ) 0.86 ( ) 0.99 ( ) 0.88 ( ) 0.98 ( ) 0.96 ( ) 0.97 ( ) 0.87 ( ) 0.90 ( ) Second Cycle of the CTT Meta-analysis: Proportional Effects on Cause-Specific Mortality Per Mmol/L LDL-C Reduction No. of deaths(% pa) Statin/moreControl/less Relative risk (CI) per mmol/L LDL-C reduction 99% or 95% CI Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:

Meta-analysis of Statin Trials: Effect of Intensive LDL-C Lowering vs Standard Statin Therapy on Fatal and Nonfatal Stroke 10 Study SEARCH IDEAL TNT ALLIANCE PROVE-IT A to Z Total: P = (heterogeneity: I 2 = 0%, P = 0.80) Conventional arm (%) RR (95% CI) 0.91 (0.77, 1.08) 0.87 (0.70, 1.08) 0.76 (0.60, 0.96) 0.90 (0.58, 1.42) 1.09 (0.59, 2.01) 0.79 (0.48, 1.29) 0.87 (0.78, 0.96) Log-scale RR (95% CI) Amarenco P et al. Lancet Neurol. 2009;8: Intensive arm (%)